The proposed research is directed at the long-term goal of gaining significant new knowledge of the functional contribution of brain monoaminergic systems to neurochemical mechanisms regulating neuronal activity during seizure discharge. The objectives include a characterization of the inhibitory role of monoaminergic involvement in seizure mechanisms and a determination of whether digitoxigenin has direct and/or indirect effects on these monoaminergic mechanisms. An assessment of brain monoaminergic involvement in electroshock convulsant thresholds and the contribution of specific brain monoamines to the effect of digitoxigenin to lower convulsant thresholds will be determined in the adult rat. This design will be extended to the young rat during postnatal brain maturation to determine the involvement of monoamines in the age-related development of seizure patterns, regulation of convulsant thresholds and effect of digitoxigenin on these parameters. The influence of repeated or continuous exposure of the postnatal maturing rat brain to digitoxigenin on monoaminergic mechanisms will be determined. In the adult rat, research will be directed at the regional brain localization of digitoxigenin, an electrographic characterization of the convulsant action of digitoxigenin and the effect of digitoxigenin on regional brain monoamine turnover rates, all related to the time course of digitoxigenin convulsions. Also, the effect of digitoxigenin on monoamine uptake and release using in vitro synaptosome systems prepared from specific brain regions will be determined. The results of the research, in a single animal species, should contribute new knowledge of the functional contribution of brain monoamines to neuronal regulation during seizure discharge.